Vaccines containing antigens from more than one pathogenic organism within a single dose are known as “multivalent” or “combination” vaccines e.g. diphtheria, tetanus & pertussis (“DTP”) vaccines and measles, mumps & rubella (“MMR”) vaccines. Combination vaccines offer patients the advantage of receiving a reduced number of injections, which leads to the clinical advantage of increased compliance (e.g. see chapter 29 of reference 1), particularly for pediatric vaccination. At the same time, however, they present difficulties due to factors including: physical and biochemical incompatibility between antigens and other components; immunological interference; and stability. Some of these difficulties can be addressed by suitable formulation of the vaccine.
DTP vaccines have previously been combined with meningococcal conjugates. For instance, reference 2 prepared a fully-liquid 8-valent D-T-Pw-HBsAg-Hib-MenC-MenW135-MenY vaccine. It also discloses vaccines prepared by mixing aqueous D-T-Pw-HBsAg components with lyophilised mixtures of meningococcal conjugates. A similar liquid/lyophilised formulation is disclosed in reference 3, where a 7-valent combination vaccine was prepared by using a liquid 4-valent D-T-Pw-HBsAg combination vaccine (TRITANRIX HEPB™) to reconstitute a lyophilised Hib-MenA-MenC conjugate component (see also references 29, 30, 76 & 99). Similarly, reference 4 prepared a 7-valent combination vaccine by using a liquid 5-valent D-T-Pa-IPV-HBsAg combination vaccine (INFANRIX PENTA™) to reconstitute a lyophilised MenC-MenY conjugate component. The concentration of antigens and adjuvant in these three documents were, per millilitre:
Ref. 2Ref. 3Ref. 4Diphtheria toxoid15 Lf15 Lf50 LfTetanus toxoid6.5 Lf6.5 Lf20 LfPertussisPw: 30 OUPw: 30 OUPa: 50 μg PT, 50 μg FHA, 16 μg PRNAl+++0.6 mg1.26 mg1.4 mgIt is an aim of the invention to provide further and improved formulations for combination vaccines that include diphtheria, tetanus, pertussis and meningococcal antigens. A further aim for some embodiments is to provide formulations that are useful for adolescent immunisation (e.g. boosters).